Our major goal is to test the effect of varying doses of dietary vitamin E on the tumorigenicity of established tumor cell lines. Inasmuch as the influence of vitamin E is often modified by the presence of polyunsaturated fatty acids (PUFA), the titration of vitamin E will be against a background of different levels of dietary PUFA. The impetus for this work has been our observation that it is possible to isolate a tumor cell varient whose tumorigenicity varies in a very different way from the original cell line upon variation of the degree of unsaturation of the fats available in the diet. The variant was isolated in vitro by growth in cell culture media which have been depleted of lipids. One of the observations has been that under some conditions vitamin E can have a protective effect against tumor at lower levels, but not at higher levels. Using these conditions, the variant tumor line is relatively unaffected by alterations in deitary vitamin E. Given these otherwise isogenic strains, it would appear that they offer an excellent model system to investigate the mode of action of fats and vitamin E on tumorigenesis. Since tumorigenicity can be affected by tumor growth rate and the host's defense mechanisms, it is our intention to study the effect of vitamin E in diets varying in PUFA levels on tumor incidence and growth, the host's immune response to tumors and the susceptibility of the tumor cells to these defense mechanisms. It is expected that this approach in an animal model will produce information useful in determining whether megadose levels of vitamin E or other lipid alterations in the diet can result in diminishing the incidence of cancer.